EP0509338A1 - Fabrication et utilisation de préparations stables de liposomes de petite taille - Google Patents
Fabrication et utilisation de préparations stables de liposomes de petite taille Download PDFInfo
- Publication number
- EP0509338A1 EP0509338A1 EP92105737A EP92105737A EP0509338A1 EP 0509338 A1 EP0509338 A1 EP 0509338A1 EP 92105737 A EP92105737 A EP 92105737A EP 92105737 A EP92105737 A EP 92105737A EP 0509338 A1 EP0509338 A1 EP 0509338A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- liposome preparation
- collagen hydrolyzate
- lecithin
- preparation according
- fatty acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
- A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/678—Tocopherol, i.e. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- liposomes are small vesicles with a bilayer structure. They are used in the pharmaceutical field as pharmaceutical carriers, e.g. for parenteral or topical application.
- Active ingredients with different chemical-physical properties can be incorporated into liposomes.
- Water-soluble active ingredients can be found in the interior of the vesicles and between the bilayer lamellae. In contrast, more lipophilic substances intercalate into the bilayer. If larger amounts of such active ingredients are therefore incorporated into liposomes, the diameter of the vesicles can increase significantly. In this case, pharmacokinetic and thus therapeutic properties can change significantly.
- Small liposomes are often advantageous because they are not recognized by the reticulo-endothelial system (RES) and are therefore not filtered out of the bloodstream in the liver or kidney. As a result, plasma levels can be maintained over a long period of time.
- RES reticulo-endothelial system
- Liposomes determined a half-life of over 20 hours (cf. J. Senior et al., Biochim. Biophys. Acta 839, 1 (1985)). This means an increased availability of an encapsulated active ingredient at the potential site of action, for example a tumor tissue. This is because the circulating liposome depot is only slowly broken down by enzymatic degradation and interaction with other blood components. The encapsulated active ingredient is released and can be available for therapeutic purposes.
- FR-A 2 591 105 describes pharmaceutical compositions based on lipid-containing multilamellar vesicles for dermatological or cosmetic use described which contain a retinoid or an analog thereof. This combination is intended to avoid irritation on the skin. Hydrogenated lipids and eg cholesterol or sitosterol are used as vesicle components. However, the liposomes produced from them have a large particle size and the associated disadvantages. Overall, small-sized particles are therefore desirable.
- the stability of the liposome preparation is also of crucial importance for its therapeutic or cosmetic use.
- the instability of liposome preparations is problematic and often limiting for therapeutic applications, on the one hand with regard to the particles themselves and on the other hand with regard to the incorporated active ingredient.
- the primary focus is on decomposing the active ingredient.
- the type and rate of decomposition are specific to each active ingredient.
- Suitable antioxidants such as butylated hydroxytoluene or vitamin E can reduce oxidative processes.
- pH-dependent hydrolysis processes can be reduced by suitable buffering.
- increased hydrolysis can occur due to the increased contact of the substance with water, but there is the possibility of stabilization by sufficient storage in the bilayer.
- the respective decomposition reaction and the physico-chemical properties of the substance are decisive for the stability of the active substance.
- liposomes themselves can be affected by lipid oxidation, lipid hydrolysis and particle aggregation.
- Lipid oxidation can be reduced by adding antioxidants as described by CA Hunt, S. Tsang., in Int.J.Pharm. 8, 101 (1981) or by AWT Konings in Liposome Technology, Vol. I.
- lecithins with saturated fatty acid esters that cannot be oxidized can be used for liposomes (see P. Kibat, dissertation, Heidelberg University 1987).
- Hydrolysis of the lecithins to lysolecithins can additionally be reduced by buffering the systems in the range from pH 6-7 (see S. Froeckjear et al., Optimization of Drug Delivery, A. Benzon Symposium 17, Copenhagen (1982)).
- a lecithin is selected as the starting material for liposome production, to which 1 to 90% fatty acid esterified collagen hydrolyzate are added.
- Soy or egg lecithin is particularly suitable as a liposome component.
- other synthetically produced or native C16-C20 phosphatidylcholines are particularly suitable, where the fatty acid content can be saturated or unsaturated. 10 to 50% of the fatty acid-esterified collagen hydrolyzate is preferably incorporated therein.
- Collagen hydrolyzate ( ⁇ KH) esterified with oleic acid is particularly preferred.
- This material is an amphiphilic surfactant that is in solid form. Although it is already used as a stabilizer in pharmaceutical and cosmetic creams, it has not yet been used to stabilize liposomes.
- the total concentration of lecithin and collagen hydrolyzate in the aqueous dispersion obtained is between 5 and 350 mg / ml, preferably between 20 and 180 mg / ml. This corresponds to about 0.5 to 35% or preferably 2-18% lecithin / collagen hydrolyzate in the liposome preparation.
- collagen hydrolyzate in particular from ⁇ KH, the liposomes produced are significantly smaller than without this additive, which has the advantages described above. This effect has not previously been achieved with liposomes containing active ingredients. A reduction in particle size can only be achieved by adding some other substances with an amphiphilic character if there is no active ingredient.
- Table 1 below shows the influence of various substances customary in liposome technology on the particle size of the liposomes produced using a high-pressure homogenizer, that is to say by the same process in each case. If, on the other hand, large liposomes are produced from soy lecithin using the shaking method (cf. AD Bangham et al., J. Mol. Biol. 13, 238 (1965)), the liposomes are clear when an amphiphilic substance is added (for example in the case of cholesterol) larger than the original particles.
- an amphiphilic substance for example in the case of cholesterol
- collagen hydrolyzate according to the invention and in particular of ⁇ KH also leads to a significant reduction in the particle size, as shown below. The influence on the particle size is therefore process-independent and only substance-dependent.
- polysorbate 80 As the only surfactant, polysorbate 80 also leads to a significant reduction in particle size, but only in the case of liposomes free from active substances (see, for example, Kronberg et al., J. Pharm. Sci., 79 (8), 667-71 (1990) Liposomes, e.g. with tocopherol nicotinate, hexachlorophene, on the other hand, the addition of polysorbate (e.g. 20%) leads to a significant increase in particle size with an additional non-uniform distribution, which is why this addition is not suitable for the production of pharmaceutically stable products.
- the vesicle size is reduced even with the simultaneous incorporation of lipophilic therapeutic agents.
- lipophilic Active ingredients for incorporation can be processed, for example, acne therapeutic agents such as hexachlorophene, tretinoin, or minocycline.
- topically applicable active ingredients such as alpha-tocopherol nicotinate, tromantadine base, croconazole, minocycline, meclocycline, cyproterone, cyproterone acetate, corticoids, 2-tert.-butyl-4-cyclohexylphenyl nicotinate-N-oxide, corticosteroids, androgeniceneroenetradiols, androgeniceneroenetradiols, androgeniceneroenetradiols, androgeniceneroenetradiols
- Non-steroidal anti-inflammatory drugs dihydropyridines, spironolactone, erythromycin esters, lipophilic local anesthetics, estradiol esters or lipophilic antihistamines are possible.
- the active substance content can vary according to the therapeutic requirements. For example, up to 50 g of active ingredient can be used per 100 g of collagen hydrolyzate esterified with fatty acid or lipid mixed with ⁇ KH. This results in the possibility of processing such active substances in liposomes with a very small diameter. Due to the general vesicle size, an increase in therapeutic activity is possible due to the small diameter.
- the already described storage stability of the liposomes is essential for a broad application of liposomes.
- the most important physical parameter for storage stability is the particle size of the vesicles.
- the aggregation of the vesicles which occurs particularly in lecithins, can be significantly reduced by a suitable addition of fatty acid-esterified collagen hydrolyzate, as demonstrated in Table 4 below in accordance with Example 2.
- Corresponding liposomes according to the invention are therefore both primarily smaller and stable when stored. Any loss of activity that may occur due to the aggregation can thus be avoided.
- the possibility of instability of the liposomes is reduced by reducing the lecithin content (due to the addition of ⁇ KH). Because only lecithin itself can be subject to the destabilizing lysolecithin formation. The associated toxic effect can thus be significantly reduced.
- Table 4 Stability of ⁇ KH-containing tocopherol nicotinate liposomes Lipid Total lipid concentration (mg / ml) Particle size [nm] after 24 (weeks) 0 4th 12 Soy lecithin (See) 100 90 ⁇ 19 96 ⁇ 23 196 ⁇ 188 274 ⁇ 191 Soy lecithin / ⁇ KH 8: 2 according to example 2 (experience) 100 49 ⁇ 14 45 ⁇ 14 44 ⁇ 10 42 ⁇ 11
- the liposomes according to the invention therefore have a significantly better storage stability than comparable liposomes without the addition of ⁇ KH.
- liposomes containing active ingredients in particular are significantly larger and more inhomogeneous than corresponding liposomes made from soy lecithin and fatty acid-esterified collagen hydrolyzate or ⁇ KH. If the liposomes are stored for four weeks, there is a clear formation of sediment, which is not acceptable for a pharmaceutical product.
- Polysorbate is therefore not suitable as an additive for active substance-containing liposomes with the aim of reducing the particle size and stabilizing the vesicles.
- the liposome dispersion is usually polymeric gel formers to increase the viscosity and thus improve it the application.
- polyacrylic acid 0.3-1.5%
- cellulose derivatives 0.2-3%)
- sodium salts of acrylic acid-acrylamide copolymers eg commercially available as Hostacerin PN73 (R) , 1-4% use
- PN73 Hostacerin PN73
- the vesicles containing fatty acid esterified collagen hydrolyzate according to the invention show only minor particle size changes after processing into polymer gels, as documented in Table 5 below.
- Table 5 Particle size change after incorporation of liposomes in Hostacerin (R) gels and subsequent storage at 21 ° C Lipid Total lipid conc. (mg / ml) Particle size before incorporation.
- the liposome preparations according to the invention can be prepared by mixing a mixture of lecithin, preferably egg or soy lecithin together with 1-90%, in particular 10-50% collagen hydrolyzate, in particular ⁇ KH, and optionally with a pharmaceutical active ingredient such as indicated above and conventional additives in an aqueous phase at a suitable pH, preferably 5-7, dispersed.
- the dispersion obtained can then preferably be comminuted and homogenized in a high-pressure homogenizer.
- the dispersion can then be mixed with customary amounts of a suitable gel former, preferably with one of those described above.
- a suitable gel former preferably with one of those described above.
- the gel is prepared in the usual known manner.
- Optional additives such as an antioxidant e.g. Vitamin E or butylated hydroxytoluene, and preservatives such as phenoxethol, sorbic acid, Kathon CG or parabens can be added in usual amounts.
- an antioxidant e.g. Vitamin E or butylated hydroxytoluene
- preservatives such as phenoxethol, sorbic acid, Kathon CG or parabens
- the active substance-containing liposome preparations produced in this way have a vesicle size of approximately 20 to 150 nm, preferably 20 to 70 nm. They are particularly suitable for topical use - depending on the active ingredient - as dermatological or cosmetic products. Compared to previously known products, there is an increase in therapeutic activity because of the lower Vesicle diameter an increased interaction with the cells takes place and also the stability of the preparation is increased, so that a long-lasting constant effectiveness is guaranteed without toxic side effects.
- preparations according to the invention can be prepared in a simple manner, and the advantages mentioned can be used if hydrogenated lipids are not used.
- lipid dispersion 900 g is treated with a high pressure homogenizer (1.1 ⁇ 108 Pa, 40 min) and then filtered through a membrane (0.45 ⁇ m).
- soy lecithin 20 g of ⁇ -tocopherol nicotinate, 7.5 g of phenoxyethanol and 37.5 g of ethanol are heated to 50 ° C. with stirring in a suitable vessel.
- the resulting lipid dispersion (750 g) is treated with a high-pressure homogenizer (1.1 ⁇ 108 Pa, 40 min) and then filtered through a membrane (0.45 ⁇ m) (cf. Table 4).
- a gel 25 g of hostacerin (R) and 2.5 g of phenoxyethanol are dispersed in a mixture of 12.5 g of ethanol and 210 g of pH 6.5 phosphate buffer. After a day of swelling, this gel concentrate is mixed with the liposome dispersion described above. After storage at 21 ° C, these liposomes have a significantly better stability than comparable liposomes without the addition of ⁇ KH (see Table 5).
- soy lecithin 100 mg of cyproterone, 10 g of phenoxyethanol and 50 g of ethanol are heated to 50 ° C. with stirring in a suitable vessel.
- the resulting lipid dispersion (990 g) is treated with a high-pressure homogenizer (1.1 ⁇ 108 Pa, 40 min) and then with a Filtered membrane (0.45 ⁇ m).
- the liposomes produced have a significantly better storage stability than comparable liposomes without the addition of ⁇ KH.
- tretinoin and 400 mg of butylated hydroxytoluene are dissolved in 50 g of ethanol in a suitable vessel with stirring.
- 80 g of lecithin, 20 g of ⁇ KH and 10 g of phenoxyethanol are dispersed in isotonic phosphate buffer pH 6.5 (802 g).
- the ethanolic solution is stirred into the aqueous phase with Ultraturrax treatment.
- the resulting dispersion (962.5 g) is treated with a high-pressure homogenizer (1.1 ⁇ 108 Pa, 40 min) and then filtered through a membrane (0.45 ⁇ m).
- the liposomes produced have a particle size of 23 ⁇ 4 nm.
- croconazole In a suitable vessel, 1 g of croconazole is dissolved in 10 g of ethanol with stirring. The ethanolic solution will with ultraturrax treatment, stirred into the aqueous phase containing lecithin, ⁇ KH, phenoxethol. The resulting dispersion is treated with a high-pressure homogenizer (1.1 ⁇ 108 Pa, 40 min) and then filtered through a membrane (0.45 ⁇ m).
- a high-pressure homogenizer 1.1 ⁇ 108 Pa, 40 min
- soy lecithin and 2.4 g ⁇ KH are dissolved in 20 ml ethanol and injected into a suitable syringe in 80 ml isotonic buffer pH 6.5. The injection is carried out in an ultrasonic bath for better distribution of the ethanolic solution. For cleaning, the dispersion is filtered through a membrane (0.45 ⁇ m). The final concentration is 4.8% lipid and 20% ethanol. With this manufacturing technique, smaller vesicles are obtained compared to pure soy lecithin liposomes (see Table 3).
- 1.0 g hexachlorophene, 0.2 g tocopherol, 2.5 g soy lecithin and 2.5 g ⁇ KH are dissolved in 20 g ethanol and by means of a suitable syringe in 74 ml citrate / phosphate buffer pH 5.5 (with 0, 2% sorbic acid / potassium sorbate) under ultrasound treatment injected.
- the dispersion is filtered through a membrane (0.45 ⁇ m).
- the final concentration is 1% hexachlorophene, 5.0% lipid and 20% ethanol, the particle size 70-135 nm.
- a gel is prepared from the liposome dispersion with 1 g of polyacrylic acid (Carbopol 984 (R) ).
- the particle size of the liposomes in the gel preparation is 100-110 nm.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4111982A DE4111982C2 (de) | 1991-04-12 | 1991-04-12 | Stabile kleinpartikuläre Liposomenzubereitungen, deren Herstellung und Verwendung |
DE4111982 | 1991-04-12 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0509338A1 true EP0509338A1 (fr) | 1992-10-21 |
EP0509338B1 EP0509338B1 (fr) | 1995-08-16 |
Family
ID=6429461
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP92105737A Expired - Lifetime EP0509338B1 (fr) | 1991-04-12 | 1992-04-03 | Fabrication et utilisation de préparations stables de liposomes de petite taille |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0509338B1 (fr) |
JP (1) | JPH0748247A (fr) |
AT (1) | ATE126430T1 (fr) |
CA (1) | CA2065579A1 (fr) |
DE (2) | DE4111982C2 (fr) |
DK (1) | DK0509338T3 (fr) |
ES (1) | ES2077904T3 (fr) |
GR (1) | GR3017147T3 (fr) |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0613685A1 (fr) * | 1993-03-02 | 1994-09-07 | Pedro Gonzalez Ensenat | Liposomes contenant le diacetate ou le digluconate de chlorhexidine |
EP0639373A1 (fr) * | 1993-08-20 | 1995-02-22 | Euroceltique S.A. | Préparations pour l'application externe d'agents antiseptiques et/ou d'agents favorisant la cicatrisation |
WO1996005808A1 (fr) * | 1994-08-20 | 1996-02-29 | Max-Delbrück-Centrum für Molekulare Medizin | Preparations liposomales unilamellaires, avec une teneur elevee en principe actif |
FR2742988A1 (fr) * | 1996-01-03 | 1997-07-04 | Oreal | Composition aqueuse contenant des vesicules lipidiques non-ioniques et au moins un pigment non-enrobe disperse dans la phase aqueuse, procede de preparation, utilisations |
WO1998007752A1 (fr) * | 1996-08-23 | 1998-02-26 | Regents Of The University Of Minnesota | Amphiphiles s'assemblant de maniere autonome et destines a la construction de structures secondaires peptidiques |
US5807581A (en) * | 1994-02-09 | 1998-09-15 | Collagen Corporation | Collagen-based injectable drug delivery system and its use |
US5863556A (en) * | 1993-08-20 | 1999-01-26 | Euro-Celtique, S.A. | Preparations for the external application of antiseptic agents and/or agents promoting the healing of wounds |
WO1999060999A1 (fr) * | 1998-05-27 | 1999-12-02 | Euroceltique S.A. | Preparations pour l'application, au niveau des voies respiratoires inferieures, d'anti-inflammatoires, notamment d'antiseptiques et/ou d'agents favorisant la guerison des blessures |
EP1509612A2 (fr) * | 2002-03-22 | 2005-03-02 | Drugtech Corporation | Systeme de distribution transcellulaire de medicaments |
WO2007115635A1 (fr) * | 2006-04-01 | 2007-10-18 | Lohmann & Rauscher Gmbh & Co. Kg | Liposomes contenant du biguanide |
US7297344B1 (en) | 1999-05-27 | 2007-11-20 | Euro-Celtique, S.A. | Preparations for the promotion of wound healing in the upper respiratory tract and/or ear |
US7300667B1 (en) | 1999-05-27 | 2007-11-27 | Euro-Celtique, S.A. | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract |
US7468194B1 (en) | 1999-05-27 | 2008-12-23 | Euro-Celtique, S.A. | Preparations for the application of anti-inflammatory agents |
EP2708264A3 (fr) * | 2012-09-13 | 2014-05-14 | PM-International AG | Préparation cosmétique bicomposant |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10128315B4 (de) * | 2001-06-12 | 2004-12-02 | Kuhs Gmbh & Co. Kg | Phospholipidische Zusammensetzung, Verwendung einer derartigen phospholipidischen Zusammensetzung sowie diese enthaltende Zubereitung |
DE10203923B4 (de) * | 2002-01-31 | 2011-06-01 | Klinipharm Gmbh | Verfahren zur Erhöhung der Wasserlöslichkeit lipophiler Wirkstoffe, Herstellung von hochkonzentrierten wässrigen Zusammensetzungen dieser Wirkstoffe, derartige Produkte und ihre Verwendung |
EP1585504A4 (fr) * | 2002-11-06 | 2009-07-15 | Azaya Therapeutics Inc | Preparations liposomales d'agents pharmaceutiques stabilisees par des proteines |
FR2870741B1 (fr) * | 2004-05-25 | 2008-03-14 | Coletica Sa | Phase lamellaires hydratees ou liposomes, contenant une monoamine grasse ou un polymere cationique favorisant la penetration intercellulaire, et composition cosmetique ou pharmaceutique la contenant. |
US8053000B2 (en) * | 2005-06-07 | 2011-11-08 | Dr. Reddy's Laboratories Limited | Compositions for drug delivery |
CA2840339A1 (fr) * | 2010-06-23 | 2011-12-29 | Brightside Innovations, Inc. | Vesicules porteuses de lecithine et leurs procedes de fabrication |
US20150182542A1 (en) | 2012-02-16 | 2015-07-02 | Brightside Innovations, Inc. | Dietary and nutritional compositions and methods of use |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1987006460A1 (fr) * | 1986-04-22 | 1987-11-05 | L'oreal | Dispersion de spherules lipidiques |
WO1990012565A1 (fr) * | 1989-04-25 | 1990-11-01 | Nattermann, A. & Cie. Gmbh | Formulations aqueuses avec phospholipides |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3161962D1 (en) * | 1980-07-01 | 1984-02-23 | Oreal | Process for obtaining stable dispersions in an aqueous phase of at least a water immiscible liquid phase, and corresponding dispersions |
FR2571963B1 (fr) * | 1984-10-24 | 1987-07-10 | Oreal | Composition a usage cosmetique ou pharmaceutique contenant des niosomes et au moins un polyamide hydrosoluble et procede de preparation de cette composition. |
FR2622104B1 (fr) * | 1987-10-22 | 1990-03-30 | Bioetica Sa | Procede de stabilisation de phases lamellaires lipidiques hydratees, par ex. de liposomes, composition de phases lamellaires lipidiques hydratees, par ex. des liposomes, stabilisees par un emploi d'un support stabilisant a base d'atelocollagene et de glycosaminoglycannes et utilisation en pharmacie ou en cosmetologie |
-
1991
- 1991-04-12 DE DE4111982A patent/DE4111982C2/de not_active Expired - Fee Related
-
1992
- 1992-04-03 DE DE59203259T patent/DE59203259D1/de not_active Expired - Fee Related
- 1992-04-03 EP EP92105737A patent/EP0509338B1/fr not_active Expired - Lifetime
- 1992-04-03 ES ES92105737T patent/ES2077904T3/es not_active Expired - Lifetime
- 1992-04-03 AT AT92105737T patent/ATE126430T1/de not_active IP Right Cessation
- 1992-04-03 DK DK92105737.8T patent/DK0509338T3/da active
- 1992-04-08 CA CA002065579A patent/CA2065579A1/fr not_active Abandoned
- 1992-04-13 JP JP4137475A patent/JPH0748247A/ja active Pending
-
1995
- 1995-08-17 GR GR950402067T patent/GR3017147T3/el unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1987006460A1 (fr) * | 1986-04-22 | 1987-11-05 | L'oreal | Dispersion de spherules lipidiques |
WO1990012565A1 (fr) * | 1989-04-25 | 1990-11-01 | Nattermann, A. & Cie. Gmbh | Formulations aqueuses avec phospholipides |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0613685A1 (fr) * | 1993-03-02 | 1994-09-07 | Pedro Gonzalez Ensenat | Liposomes contenant le diacetate ou le digluconate de chlorhexidine |
EP0639373A1 (fr) * | 1993-08-20 | 1995-02-22 | Euroceltique S.A. | Préparations pour l'application externe d'agents antiseptiques et/ou d'agents favorisant la cicatrisation |
US5863556A (en) * | 1993-08-20 | 1999-01-26 | Euro-Celtique, S.A. | Preparations for the external application of antiseptic agents and/or agents promoting the healing of wounds |
US5807581A (en) * | 1994-02-09 | 1998-09-15 | Collagen Corporation | Collagen-based injectable drug delivery system and its use |
WO1996005808A1 (fr) * | 1994-08-20 | 1996-02-29 | Max-Delbrück-Centrum für Molekulare Medizin | Preparations liposomales unilamellaires, avec une teneur elevee en principe actif |
US6399094B1 (en) | 1994-08-20 | 2002-06-04 | Martin Brandl | Unilamellar liposomal preparations with high active substance content |
US6146660A (en) * | 1996-01-03 | 2000-11-14 | L'oreal | Aqueous composition containing nonionic lipid vesicles and at least one uncoated pigment dispersed in an aqueous phase, process for preparation and use thereof |
FR2742988A1 (fr) * | 1996-01-03 | 1997-07-04 | Oreal | Composition aqueuse contenant des vesicules lipidiques non-ioniques et au moins un pigment non-enrobe disperse dans la phase aqueuse, procede de preparation, utilisations |
EP0782847A1 (fr) * | 1996-01-03 | 1997-07-09 | L'oreal | Compositions aqueuses contenant des vésicules lipidiques non-ioniques et au moins un pigment non-enrobé dispersé dans la phase aqueuse, procédé de préparation, utilisations |
US5972378A (en) * | 1996-01-03 | 1999-10-26 | L'oreal | Aqueous composition containing nonionic lipid vesicles and at least one uncoated pigment dispersed in an aqueous phase, process for preparation and use thereof |
WO1998007752A1 (fr) * | 1996-08-23 | 1998-02-26 | Regents Of The University Of Minnesota | Amphiphiles s'assemblant de maniere autonome et destines a la construction de structures secondaires peptidiques |
US6096863A (en) * | 1996-08-23 | 2000-08-01 | Regents Of The University Of Minnesota | Self-assembling amphiphiles for construction of peptide secondary structures |
WO1999060998A1 (fr) * | 1998-05-27 | 1999-12-02 | Euroceltique S.A. | Preparations pour l'application d'anti-inflammatoires, et plus particulierement d'antiseptiques et/ou d'agents favorisant la guerison des blessures, dans les voies respiratoires superieures et/ou l'oreille |
WO1999060999A1 (fr) * | 1998-05-27 | 1999-12-02 | Euroceltique S.A. | Preparations pour l'application, au niveau des voies respiratoires inferieures, d'anti-inflammatoires, notamment d'antiseptiques et/ou d'agents favorisant la guerison des blessures |
US7297344B1 (en) | 1999-05-27 | 2007-11-20 | Euro-Celtique, S.A. | Preparations for the promotion of wound healing in the upper respiratory tract and/or ear |
US7300667B1 (en) | 1999-05-27 | 2007-11-27 | Euro-Celtique, S.A. | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract |
US7468194B1 (en) | 1999-05-27 | 2008-12-23 | Euro-Celtique, S.A. | Preparations for the application of anti-inflammatory agents |
EP1509612A2 (fr) * | 2002-03-22 | 2005-03-02 | Drugtech Corporation | Systeme de distribution transcellulaire de medicaments |
EP1509612A4 (fr) * | 2002-03-22 | 2005-07-20 | Drugtech Corp | Systeme de distribution transcellulaire de medicaments |
WO2007115635A1 (fr) * | 2006-04-01 | 2007-10-18 | Lohmann & Rauscher Gmbh & Co. Kg | Liposomes contenant du biguanide |
EP2708264A3 (fr) * | 2012-09-13 | 2014-05-14 | PM-International AG | Préparation cosmétique bicomposant |
Also Published As
Publication number | Publication date |
---|---|
ATE126430T1 (de) | 1995-09-15 |
ES2077904T3 (es) | 1995-12-01 |
DE59203259D1 (de) | 1995-09-21 |
DK0509338T3 (da) | 1995-09-18 |
DE4111982C2 (de) | 1998-12-24 |
EP0509338B1 (fr) | 1995-08-16 |
CA2065579A1 (fr) | 1992-10-13 |
JPH0748247A (ja) | 1995-02-21 |
GR3017147T3 (en) | 1995-11-30 |
DE4111982A1 (de) | 1992-10-15 |
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